Prostaglandins are a group of lipids, which are modified fatty acids attached to a 5-membered ring and with biological/pharmaceutical activities suitable for a variety of therapeutic uses. Such uses include reproductive health disorders and disorders linked to inflammatory response. However, prostaglandins are often unstable under ambient conditions and have sometimes proved difficult to store and produce in a form suitable for pharmaceutical/therapeutic use.
A prostaglandin formulation, which allows controlled release of the active compound for therapeutic use is described in patent specifications GB 2047093 and GB 2047094. Such formulations use hydrogels, which are known sustained release delivery vehicles; and in particular, “solid” cross-linked polyurethane materials having the ability to swell and absorb several times their own weight of water whilst retaining their physical integrity. The formulations have been provided as pessaries to deliver dinoprostone (a PGE2 prostaglandin) to the cervix to ripen it prior to the induction of labour, and is available under the trademarks Propess® and Cervidil®. The pessary is enclosed in a net pouch and usually remains in place in the cervix for up to 24 hours. However, this prostaglandin, even when loaded into such hydrogels, is somewhat unstable at room temperature and therefore the pessary is generally stored at temperatures of around −20° C.
Various attempts have been made to provide stabilised formulations of prostaglandins in general. PGE2 prostaglandins tend to be more unstable than PGE1 prostaglandins.
Misoprostol is a synthetic prostaglandin analogue; in particular, a cytoprotective prostaglandin PGE1 analogue. Misoprostol is a compound represented by the following stereoisomeric formulae:

Misoprostol in its physical state is an oil, which is difficult to formulate and unstable at room temperature. Misoprostol possesses mucosal protective properties and is an inhibitor of gastric acid secretion. Misoprostol has been used previously in the treatment and prevention of gastric ulcers, in particular NSAID-induced ulcers.
Misoprostol may be obtained commercially or prepared by known reaction schemes, such as by the methods taught in U.S. Pat. No. 3,965,143, for example.
U.S. Pat. No. 4,301,146 describes a solid state dispersion of misoprostol and polyvinyl pyrrolidone (PVP) or hydroxypropylmethylcellulose (HPMC). These formulations may be in the form of a tablet or capsule.
U.S. Pat. No. 5,935,939 describes a stabilised solid state dispersion of misoprotol and in particular, the preparation of stabilised misoprostol using amorphous or semi-crystalline excipients.
U.S. Pat. No. 6,642,274 discloses use of a large number of prostaglandins, including misoprostol. However, there is no focus on the problems of formulating misoprostol. Hydrogels are mentioned but these are semi-liquid compositions or low melting compositions suitable for suppositories.
US Patent Publication 2003/0050620 discloses prostaglandins in general but not PGE1 analogues. Hydrogels are mentioned but the problems of formulating PGE1 analogues are not addressed.
Other patent publications dealing with prostaglandins and/or hydrogel carriers include U.S. Pat. No. 6,287,588, U.S. Pat. No. 6,589,549, US 2002/0076441, U.S. Pat. No. 6,685,962, US 2003/0021845, US 2003/0049320 and US 2003/0064088.
It is an object of the present invention to provide a PGE1 formulation showing increased stability properties compared with unformulated misoprostol; and in particular to provide a solid state misoprostol formulation which has increased storage stability at room temperature.